In light of the fact that patients with newly diagnosed Type I and Type II diabetes have significantly elevated basal and exercise- induced growth hormone (GH) levels despite their hyperglycemia, this proposal aims to continue the study of the effects of insulin on in vitro GH gene expression. Insulin action will be studied on the regulation of basal and stimulated GH gene transcription, mRNA levels and protein synthesis. Specific regulatory sites for insulin action will also be identified on the transfected GH gene. Insulin binding and receptor occupancy will be correlated with biologic action of insulin on GH gene expression. Increased GH levels have been implicated in development of diabetic macrovascular and microvascular complications. The elevations of GH have also been implicated in the pathophysiology of metabolic disorder in diabetes. The studies proposed here will provide further insight into the molecular mechanism of insulin action at the level of specific polypeptide hormone gene regulation.